The major purpose of this project is to identify those factors in hemorrhagic shock which make animals and man unresponsive to therapy, with the object of determining new modes of treatment for patients. With this objective in mind, we are proposing three major lines of investigation: (1) Prostaglandin E1 has proven highly effective in our hands during the normovolemic phase of hemorrhagic shock in rats and dogs. We have therefore proposed to extend this study to primates to determine if this drug is equally effective in a species closely related to man. (2) Since death from hemorrhagic shock does not necessarily occur in the immediate shock period, but may overtake the patient a day or more after the period of major hypotension, we plan to obtain a better definition of metabolic state of animals in the first week after shock as well as in the first few hours. Most previous research in terms of metabolic changes has been confined to at most the first 24 hours. (3) Current data suggest that new therapeutic approaches for shock may be discovered through manipulation of the anaerobic glycolytic cycle to the Krebs cycle. Clues to such enzyme alterations may be found in animal models from species which are known to tolerate anoxia much better than man. Such species are found in the diving mammals, and evaluation of the shock state in nutria, a diving mammal, is proposed.